Process of producing amino-arylthiazole-compounds



Patented June 4, 1935 UNITED STATES PATENT OFFICE PROCESS ,OF PRODUCINGAMINO-ARIEL- THIAZOLE-COMPOUNDS Richard Herz, Frankfort-on-the-Main, andMax Schubert,

Frankfort on the Main Fechenheim, Germany, assignors to General AnilineWorks, Inc., New York, N. Y., a corporation of Delaware No Drawing.Application June 1,1931, Serial No. 541,534. In Germany January 26, 1929Claims.

5 lar use of disulfurdichlorlde (S2612) in the process'for producingamino-thiazoles of the general formula:

, X wherein X meanshydrogen or methyl, Y means hydrogen or methyl oraralkyl or halogen when starting from the urea-derivatives of thegeneral formula:

wherein X and Y have the aforesaid signification. In this processdisulfurdichloride is a particularly suitable agent for effecting thering closure.

Whereas Hugershofi only used chloroform as diluent-for the action ofbromine, it is possible to use for the present process other organicdiluents more usual forv technical manufacture, such as chlorobenzene,carbon-tetrachloride or glacial acetic acid. 3 V p The specialimprovement involved by our present process consists in the factthat-the reaction products are free from by-products which otherwise areformed to some degree by a simultaneous entranceofchlorine atoms intothe nucleus of the formed aminothiazole compound. The sulfur formed bythe reaction remains either dissolved in the solvent applied or may beremoved from the reaction products in the usual manner, for instance itmay be separated by filtration from the solution of the hydrochloride ofthe aminothiazole. The reaction products are then immediately suitablefor technical use.

In order to further illustrate our invention the following examples aregiven, the parts being by weight and all temperatures in centigradedegrees, but it is however to be understood, that our invention is notlimited to the particular products nor reacting conditions mentionedtherein.

Example 1 5 parts of -ethoxy-phenyl-thio-urea (of. J our- (cram-44) nalfiir praktische' Chemie, vol. 65, page 379) are suspended in about 50parts of chlorobenzene and at room temperature while stirring 5.2 partsof disulfurdichloride (S2012) areadded. Withweakly warming thecomponents are dissolved. Advantageously the solution is warmed for somehours on the water bath, then the mass is allowed to stand for somehours and the separated precipitate is filtered on and dried. It isdissolved in cold water and by adding a caustic soda solution to theaqueous solution the free l-amino- 5-ethoxy-benzothiazole of theformula:

is obtained. It melts when re benzene at 160-163".

' Example 2 20 17 to 20 parts of disulfurdichloride (SzClz) aredissolved in about parts; of chlorobenzene and; at about 90 a suspensionof 16.4 parts of l-methylphenyl-thiourea in '20 'to 30 parts ofchlorobenzene is allowed to run in. The mixture is then heated for somehours at ill-. When cooled down the separated reaction product isfiltered off and dried. It is dissolved in cold water, to whichadvantageously a little quantity of hydrochloric acid has been added.From the solution of the hydrochloride of 5-methyl-laminobenzothiazolethus obtained some quantities of separated sulfur are removed byfiltration, and the free base is isolated from the solution of thehydrochloride by adding the corresponding amount of for instance acaustic soda solution. The 1-amino-5-methyl-benzothiazole of theformula:

crystallized from CHs- S melts in a pure state at 142. 45

Example 3 20 parts of 2-methyl-4-chlorophenyl-thiourea are suspended inabout 200-250 parts of carbon tetrachloride and to this suspension atroom temperature 20-25 parts of disulfurdichloride (S2012) are added.Then the mixture is heated while well stirring for some hours in anapparatus provided with a reflux condenser. When cool the reactionproduct is filtered off and converted into 55 the free base in themanner described in the foregoing example. The 1-amino-3-methyl-5-chlorobenzothiazole of the formula:

01- s r r O-NH:

CH3 thus obtained melts in a pure state at 203205.

Example 4 thus formed represents colorless needles of 138 melting point.

" We claim:

1. A process for producing amino-thiazolecompounds of the generalformula:

wherein X means hydrogen or methyl, Y means hydrogen, methyl or alkoxyor Y is halogen when X represents methyl, which process comprises actingwith disulfurdichloride (S2C12) on thiourea-derivatives of the generalformula:

NH-OSNH:Y

X wherein X and Y have the aforesaid signification.

2. A process for producing 3-methyl-5-chlorol-aminobenzothiazole of theformula:

which process comprises acting with disulfurdichloride (S2C12) on2-methyl-4-chlorophenylthio-urea of the formula:

NEE-O S-NH:

3. A process for producing S-methyl-l-aminobenzothiazole of the formula:

mo- -s CNH2 which process comprises acting with disulfurdichloride(S2012) on 4- tolylthiourea of the formula:

4. A process for producing 5-alkoxy-1-aminobenzothiazole-compounds ofthe formula:

which process comprises acting with sisulfurdichloride (S2012) on4-alkoxyphenyl-thio-urea of the formula:

5. A process for producing 5-ethoxy-1-aminobenzothiazole of the formula:

which process comprises acting at room temperature and subsequently onthe water bath with 5.2 parts of disulfurdichloride on 5 parts of4-ethoxy-phenyl-thio-urea in presence of 50 parts of chlorobenzene andisolating the free 2-amino-S-ethoxy-benzothiazole by adding a causticsoda solution to the aqueous solution of the hydrochloride primarilyformed.

RICHARD HERZ. MAX SCHUBERT.

